The purpose of this project is to analyze the hormonal control of calcium metabolism during pregnancy, intra-uterine growth, and postnatal development. In particular these studies focus on the role of the vitamin D-endocrine system. An important role for vitamin D in developmental and reproductive biology is indicated by documented alterations in vitamin D metabolism and tissue responses during pregnancy, lactation, and postnatal development. A role of vitamin D in controlling placental and yolk sac function is suggested by the finding in both tissues of calcium binding protein (CaBP) identical to the vitamin D-dependent CaBP in intestine. This concept is further supported by recent evidence that the placenta and yolk sac contain receptors for 1,25-dihydroxycholecalciferol. In other studies, we and others have found a vitamin D-independent effect of estrogens on uterine CaBP in vivo. Experiments are designed to directly assess whether placenta and yolk sac are target tissues for vitamin D metabolite action. This will be accomplished using (1) in vitro organ culture, (2) early mouse embryo culture and (3) in vivo nutritional deprivation of vitamin D to determine the effects of vitamin D metabolites, and of estrogens, upon placental and yolk sac CaBP. The cellular and subcellular localizations of immunoreactive CaBP will be determined using immunohistological techniques at both the light and electron microscope level. The CaBP developmental defects that we have recently discovered in the intestine of juvenile X-linked hypophosphatemic (Hyp) mice will be characterized by comparing the developmental induction of kidney CaBP and intestinal CaBP. These experiments will determine whether the developmental defect that we have observed in Hyp intestinal CaBP is also present in Hyp kidneys. The integrity of Hyp renal and intestinal responses to vitamin D will be determined by measuring the effects of 1,25(OH)2D injections on the concentrations of CaBP in the kidney and intestine. Characterization of ATP-dependent calcium uptake in vesicles of small intestinal basal-lateral membranes will be studied with respect to vitamin D requirement, the time course of D action and the potential role of vitamin D-dependent CaBP in the Ca uptake. The post-natal developmental pattern of the Ca uptake will be compared to the post-natal changes in Ca absorption. These studies promise to increase our understanding of physiologic processes of the perinatal period and to provide tools for the study of their pathologic alterations.